Anti-migration micropatterned stent coating

ABSTRACT

An endoprosthesis has an expanded state and an unexpanded state, the endoprosthesis includes a stent, wherein the stent has a first end, a second end, an inner surface defining a lumen, an outer surface, and a thickness defined between the inner surface and the outer surface; and a stent end covering disposed at one of the first and second ends, the stent end covering including a polymeric coating that includes a base and a plurality of protrusions, the base including a first major surface facing the outer surface of the stent, the base further including a second major surface from which each of the plurality of protrusions extends outwardly, the first major surface opposing the second major surface, wherein the protrusions are arranged in a micropattern. Methods of making and using an endoprosthesis are provided.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/210,979, filed Mar. 14, 2014, which claims the benefit of provisionalU.S. Patent Application No. 61/798,685, filed on Mar. 15, 2013), whichis hereby incorporated by reference in its entirety.

The following patent applications are incorporated herein by reference,each in its entirety:

U.S. Patent Application No. 61/798,897 (Seddon et al.), entitledANTI-MIGRATORY STENT COATING, filed on Mar. 15, 2013;

U.S. Patent Application No. 61/798,794 (Clerc), entitled DELIVERY DEVICEFOR PARTIALLY UNCONSTRAINED ENDOPROSTHESIS, filed on Mar. 15, 2013;

U.S. Patent Application No. 61/799,312 (Fleury et al.), entitledSUPERHYDROPHOBIC COATING FOR AIRWAY MUCUS PLUGGING PREVENTION, filed onMar. 15, 2013;

U.S. Patent Application No. 61/798,545 (Leanna et al.), entitled MEDICALDEVICES HAVING MICROPATTERN, filed on Mar. 15, 2013; and

U.S. Patent Application No. 61/798,991 (Bertolino et al.), entitledBIOPSY TOOL HAVING MICROPATTERN, filed on Mar. 15, 2013.

BACKGROUND OF THE INVENTION

A stent is a medical device introduced into a body lumen and is wellknown in the art. A stent may be delivered in an unexpanded state to adesired location in a bodily lumen and then expanded by an internalradial force. Stents, grafts, stent-grafts, vena cava filters,expandable frameworks, and similar implantable medical devices,collectively referred to hereinafter as stents, have included radiallyexpandable endoprostheses, which have been used as intravascularimplants capable of being implanted transluminally.

Esophageal stents have been used to treat patients suffering from arange of malignant and non-malignant diseases. Most commonly, esophagealstents have been associated with the treatment of esophageal cancers.Esophageal stents have also been used to reduce symptoms resulting fromnon-esophageal tumors that grow to obstruct the esophagus and to treatbenign esophageal disorders, including but not limited to refractorystrictures, fistulas and perforations. In each of these cases,esophageal stents may provide mechanical support to the esophageal walland may maintain luminal patency. Because of the structure of theesophagus and conditions such as peristalsis, esophageal stents havebeen prone to stent migration.

One way to reduce the risk of stent migration has been to expose baremetal portions of the stent to esophageal tissue. The open, braidedstructure of the stent may provide a scaffold that promotes tissueingrowth into the stent. This tissue ingrowth may aid anchoring thestent in place and may reduce the risk of migration. In some cases,however, tissue ingrowth has been known to lead to reocclusion of theesophagus. In addition, esophageal stents anchored by tissue ingrowthcannot be moved or removed without an invasive procedure. To reducetissue ingrowth, stents have been covered with a coating (e.g., made ofa polymer, etc.) to create a physical barrier between the lumen and theesophageal wall. However, in some circumstance, such stents can have anunacceptable occurrence of migration, as compared to bare metalcounterparts.

Another way to reduce the risk of stent migration has been to use aflared stent in the esophagus. However, stents having flares can have anunacceptable occurrence of migration.

Granulation tissue caused by stents (e.g., endoprostheses) may occur dueto repeated trauma to a wall of a body lumen (e.g., a gastrointestinalwall, a tracheal wall, etc.) and due to subsequent lack of proper woundhealing. In some circumstances, granulation tissue, especially inexcess, can not only impede flow of solids and/or fluids (e.g., liquidand vapor) through the body lumen (e.g., mucous clearance, air movement,fluid movement, etc.) due to the reduction in the body lumencross-sectional area (e.g., reduction in radius, etc.), but also becausethe granulation tissue has a tendency to latch onto the endoprosthesis,which may increase the difficulty of removing the endoprosthesis whennecessary. Physician preference has trended toward endoprostheses thatare removable and atraumatic.

Improved stents with, for example, improved resistance to migration,improved stent adhesion to the esophageal wall, and/or improvedremovability are desired. Previous tracheal stents, such as thosediscussed in US Patent Publication Nos. 2006/0069425 and 2009/0062927,which are incorporated by reference herein in their entireties, haveincorporated bumps or other surface features into the stent itself.Another tracheal stent described in co-owned US Patent Publication No.2012/0035715, which is incorporated by reference herein in its entirety,also provides a plurality of surface protrusions on the outer surface ofthe stent.

Without limiting the scope of the present disclosure, a brief summary ofsome of the claimed embodiments is set forth below. Additional detailsof the summarized embodiments of the present disclosure and/oradditional embodiments of the present disclosure may be found in theDetailed Description of the Invention below. A brief abstract of thetechnical disclosure in the specification is also provided. The abstractis not intended to be used for interpreting the scope of the claims.

BRIEF SUMMARY OF THE INVENTION

The present disclosure provides an endoprosthesis where a preferablypolymeric coating has a number of surface features such as protrusionsthat are arranged in a micropattern.

In at least one embodiment, an endoprosthesis, having an expanded stateand a contracted state, includes a stent with a polymeric coatingadhered to an outer surface of the stent. The stent has an inner surfacedefining a lumen. In at least one embodiment, the stent is a flaredstent. The polymeric coating includes a base and a plurality ofprotrusions (e.g., micropillars, etc.) extending outwardly from thebase. In at least one embodiment, the protrusions are arranged in amicropattern. When the endoprosthesis is expanded to the expanded statein a lumen defined by a vessel wall, the micropillars apply a force thatcreates an interlock between the vessel wall and the endoprosthesis.

The micropattern is specifically designed for a particular tissue inorder to effectively interlock the stent with the tissue. In at leastone embodiment, the micropattern is present along at least a portion ofthe endoprosthesis. In at least one embodiment, the protrusions of themicropattern can be uniform or the micropattern can be formed ofprotrusions having a first configuration and protrusions having at leasta second configuration.

The protrusions may be micropillars and may be selected from a groupincluding cylinders, rectangular prisms, and similar structures. In atleast one embodiment, the protrusions of the micropattern arecylindrical micropillars, each cylindrical micropillar having a diameterand a height, wherein the diameter of each cylindrical micropillar isequal to its height. In at least one embodiment, the cylindricalmicropillar has a lateral surface, wherein the lateral surface of thecylindrical micropillar is separated from the lateral surfaces of anadjacent micropillar by a distance greater than the diameter of thecylindrical micropillar. In at least one embodiment, the micropattern isa grid pattern.

In at least one embodiment, each protrusion of the micropattern has afirst dimension and a second dimension, wherein the first dimension isbetween about 1 μm and 100 μm, wherein the second dimension is betweenabout 1 μm and 100 μm, and wherein each protrusion is spaced apart froman adjacent protrusion by a distance, wherein a ratio between thedistance and the first dimension is between about 2.1 and 2.4. In atleast one embodiment, each protrusion has a ratio between the firstdimension and the second dimension that is between about 1 and 1.3.

In at least one embodiment, the endoprosthesis is retrievable by, forexample, a retrieval loop at a distal end of the stent.

In at least one embodiment, an endoprosthesis may include one or moreendoprosthesis ends having a covering attached thereto having amicropatterned surface that may extend circumferentially around at leasta portion of an endoprosthesis end and may extend longitudinally beyondan endoprosthesis end in a cantilever configuration. In one or moreembodiments, the cantilevered portion of the endoprosthesis end coveringmay extend beyond the stent end by a distance that is at least two times(e.g., at least three times, at least four times, etc.) the thickness ofthe cantilevered portion or the thickness may be less than two times(e.g., less than one times, less than one-half of) the thickness of thecantilever portion. In at least one embodiment, an endoprosthesis endcovering having a micropatterned surface may be deployed in a body lumenseparately from an endoprosthesis, wherein the endoprosthesis endcovering may be deployed in a body lumen followed by deployment of anendoprosthesis wherein an endoprosthesis end is disposed within at leasta portion of the endoprosthesis end covering (e.g., the endoprosthesisend covering may be biased between the endoprosthesis end and the wallof the body lumen).

Several methods of manufacturing an embodiment of the endoprosthesis areprovided. One method of manufacturing includes forming a polymericcoating, wherein the polymeric coating includes a base and a pluralityof protrusions extending outwardly from the base in a micropattern;providing a stent having an inner surface defining a lumen and an outersurface; and adhering the base of the polymeric coating to the outersurface of the stent. The polymeric coating can be formed using a moldhaving an inverse of the micropattern and injecting a polymeric materialinto the mold and, in some cases applying temperature or pressure to themold, before the polymeric material cures; using soft lithographytechniques, or by etching the polymeric coating from a layer of thepolymeric material. In at least one embodiment, an adhesive layer isapplied to at least one of a surface of the base and the outer surfaceof the stent. In at least one embodiment, the polymeric coating isformed as a tubular structure. In one or more embodiments, the polymericcoating is formed in a strip, which is wrapped (e.g., helically wrapped,circumferentially wrapped, randomly wrapped, etc.) about the outersurface of the stent.

In at least one embodiment, an endoprosthesis may have an expanded stateand an unexpanded state, the endoprosthesis including a stent, whereinthe stent has a first end, a second end, an inner surface extending fromthe first end to the second end and defining a lumen, an outer surfaceextending from the first end to the second end, and a thickness definedbetween the inner surface and the outer surface; and a stent endcovering disposed at one of the first and second ends, the stent endcovering including a polymeric coating comprising a base and a pluralityof protrusions, the base comprising a first major surface facing theouter surface of the stent, the base further comprising a second majorsurface from which each of the plurality of protrusions extendsoutwardly, the first major surface opposing the second major surface,wherein the protrusions are arranged in a micropattern.

In one or more embodiments, the stent end covering is adhered to theouter surface of the stent, the inner surface of the stent, or both. Inone or more embodiments, the stent end covering extendscircumferentially and entirely around one of the first and second endsof the stent. In at least one embodiment, stent end covering extendscircumferentially and partially around one of the first and second ends.In one or more embodiments, the stent end covering extendslongitudinally from a location between the first and second ends to alocation that is not between the first and second ends. In at least oneembodiment, at least a first portion of the stent end covering has aradial thickness greater than the thickness of the stent at the stentend that is nearest to the stent end covering. In some embodiments, atleast a second portion of the stent end covering has a radial thicknessless than the radial thickness of the first portion of the stent endcovering. In at least one embodiment, an endoprosthesis may include afirst stent end covering and a second stent end covering, wherein one ofthe first and second stent end coverings is disposed at the first end ofthe stent and one of the first and second stent end coverings isdisposed at the second end of the stent.

In one or more embodiments, a method of manufacturing an endoprosthesisincludes forming a stent end covering that includes a polymeric coating,wherein the polymeric coating includes a base and a plurality ofprotrusions, the base including a first major surface facing the outersurface of the stent, the base further including a second major surfacefrom which each of the plurality of protrusions extends outwardly, thefirst major surface opposing the second major surface, wherein theprotrusions are arranged in a micropattern; the method also includingproviding a stent having a first end, a second end, an inner surfaceextending from the first end to the second end and defining a lumen, anouter surface extending from the first end to the second end, and athickness defined between the inner surface and the outer surface; themethod also including contacting the stent end covering with one of thefirst and second ends of the stent.

In one or more embodiments, the contacting further includes contactingthe stent end covering with the outer surface of the stent. In one ormore embodiments, the contacting further includes contacting the stentend covering with the inner surface of the stent. In at least oneembodiment, the contacting includes disposing the stent end coveringcircumferentially and entirely around one of the first and second ends.In one or more embodiments, the contacting includes disposing the stentend covering wherein the stent end covering extends longitudinally froma location between the first and second ends of the stent to a locationthat is not between the first and second ends of the stent. In someembodiments, the method further includes disposing the stent endcovering within a body lumen, wherein disposing the stent end coveringwithin the body lumen occurs before contacting the stent end coveringwith one of the first and second ends of the stent. In one or moreembodiments, the contacting includes deploying the stent within the bodylumen, wherein the stent end covering is disposed between a lumen wallof the body lumen and one of the first and second ends of the deployedstent. In some embodiments, forming the stent end covering including thepolymeric coating includes using a mold having an inverse of themicropattern and injecting a polymeric material into the mold. In atleast one embodiment, the contacting includes applying an adhesive to atleast one of a surface of the base and the outer surface of the stent.

In one or more embodiments of the present disclosure, a method of usingan endoprosthesis includes providing a stent end covering that includesa polymeric coating, wherein the polymeric coating includes a base and aplurality of protrusions, the base including a first major surfacefacing the outer surface of the stent, the base further including asecond major surface from which each of the plurality of protrusionsextends outwardly, the first major surface opposing the second majorsurface, wherein the protrusions are arranged in a micropattern; themethod further including providing a stent having a first end, a secondend, an inner surface extending from the first end to the second end anddefining a lumen, an outer surface extending from the first end to thesecond end, and a thickness defined between the inner surface and theouter surface; disposing the stent end covering within a lumen; andafter disposing the stent end covering within a lumen, contacting thestent end covering with one of the first and second ends of the stent.In some embodiments, the contacting includes deploying a stent withinthe lumen.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 shows a plan view of the endoprosthesis of the presentdisclosure.

FIG. 2 shows a cross-section of the endoprosthesis shown in FIG. 1.

FIG. 3 is an enlarged view of the polymeric coating of theendoprosthesis shown in FIG. 1.

FIG. 4 shows a cross-section of a portion of the polymeric coating shownin FIG. 3.

FIGS. 5-7 show cross-sections of portions of embodiments of thepolymeric coating.

FIGS. 8A-8J show cross-sections of the micropillars of the polymericcoating shown in FIGS. 3-6.

FIGS. 9A-9J show plan views of embodiments of the polymeric coatingshown in FIG. 3.

FIG. 10A shows an embodiment of the polymeric coating of the presentdisclosure.

FIG. 10B shows an embodiment of the polymeric coating of the presentdisclosure.

FIG. 11 is a view of the stent and polymeric coating during one methodof manufacturing the endoprosthesis.

FIG. 12 is a view of the stent and polymeric coating during one methodof manufacturing the endoprosthesis.

FIGS. 13A-13D are schematics showing at least one embodiment of a stentend covering.

FIGS. 14A-14B are schematics of at least one embodiment of a stent endcovering that may be implanted before a corresponding stent.

FIG. 15 depicts a perspective view of micropillars having an anchor tip.

FIG. 16 depicts a schematic of a micropillar having a swellable anchortip (e.g., before swelling).

FIG. 17 depicts a schematic of a micropillar having a swellable anchortip (e.g., after swelling).

FIG. 18 depicts a schematic of a wound patch (including one or moremicropatterns) placed over a wound.

FIGS. 19A-19C depict three example wound patches, each having adifferent arrangement of adhesive micropatterned polymer coating(s) andwound-covering micropatterned polymer coating(s).

FIGS. 20A-20C depicts a schematic of the method of deploying a woundpatch using a tubular delivery system, such as an endoscope.

DETAILED DESCRIPTION OF THE INVENTION

While the subject matter of the present disclosure may be embodied inmany different forms, there are described in detail herein specificpreferred embodiments of the present disclosure. This description is anexemplification of the principles of the present disclosure and is notintended to limit the present disclosure to the particular embodimentsillustrated.

For the purposes of this disclosure, like reference numerals in thefigures shall refer to like features unless otherwise indicated. Areference numeral that includes a letter (e.g., 50A, 50B, etc.) shall beconsidered to be a like reference numeral. For example, polymer coating50, stent end covering 50A, and stent end covering 50B all have likereference numerals and refer to like features unless otherwiseindicated.

The present disclosure relates to micropatterned polymeric coatings foruse on medical devices. In some embodiments, the micropatternedpolymeric coatings are utilized with implantable medical devices, suchas stents, to reduce or prevent stent migration, particularly for stentsused in the gastroesophageal system, including, but not limited to,esophageal, biliary, and colonic stents. The stents described in thisapplication may also be used in the trachea, the cardiovascular system,and elsewhere in the body (e.g., any body lumen). The present disclosurealso relates to micropatterned polymeric coatings to be applied to, forexample, stent ends, which may reduce trauma, promote wound healing, andreduce or avoid granulation tissue buildup.

FIGS. 1 and 2 show an esophageal endoprosthesis 20 of the presentdisclosure with a proximal end 22 and a distal end 24. Theendoprosthesis 20 includes an expandable stent 40 and a polymericcoating 50. Expandable stent 40 can be self-expanding, balloonexpandable, or hybrid expandable. Embodiments of the expandable stent 40contemplate stents having a constant diameter, tapers, flares and/orother changes in diameter in the body and/or at an end. The expandablestent 40 has an inner surface 42, an outer surface 44, a first end 46and a second end 48, and the polymeric coating 50 is disposed about atleast a portion of the outer surface 44. In at least one embodiment, thepolymeric coating 50 substantially covers the entire outer surface 44 ofthe expandable stent 40. In other embodiments, the polymeric coating 50covers a portion of the outer surface 44 of the expandable stent 40. Asshown in FIG. 2, the polymeric coating 50 can be directly connected tothe outer surface 44 of the expandable stent 40. In one or moreembodiments, the polymeric coating 50 can be connected to the outersurface 44 of the expandable stent 40 using an adhesive or other meansof attaching the coating to the device. In at least one embodiment, thepolymeric coating at least partially covers the inner surface 42 also.In at least one embodiment, partial coverage can include partialcoverage of the perimeter and/or the length. In some embodiments, thepolymer coating 50 and the stent 40 can be integral (e.g., collectivelyformed as an integral construction). For example, in one or moreembodiments in which at least a portion a stent 40 is made of a material(e.g., silicone, silicone coating, biocompatible polymer or metal, etc.)appropriate for micropatterning, then the micropattern may be directlyincorporated into the structure of the stent 40 (e.g., the stent 40 andpolymer coating 50 having a micropattern can be integrally formed).

In at least one embodiment, shown in FIGS. 2 and 3, the polymericcoating 50 includes a base 52 and a plurality of protrusions, such asmicropillars 54, extending outwardly from the base 52. In at least oneembodiment, the micropillars are seamlessly incorporated into the baseof the coating. In at least one embodiment, the base 52 is coterminouswith the expandable stent 40. What is meant by “coterminous” is that thebase 52 of the polymer coating 50 and the expandable stent 40 have thesame boundaries, cover the same area, and are the same in extent. Inother words, the expandable stent 40 and the base 52 each have first andsecond ends, and the expandable stent 40 and the base 52 extend betweentheir first and second ends. The first end of the expandable stent 40 isthe same as first end of the base 52, and the second end of theexpandable stent 40 is the same as the second end of the base 52. Sincethe expandable stent 40 and the base 52 extend between their first andsecond ends, the expandable stent 40 and the base 52 have the sameboundaries, cover the same area, and are the same in extent. Thus, thebase 52 and the expandable stent 40 are coterminous. The expandablestent 40 and the base 52 therefore are coterminous in at least oneembodiment. Also, base 52 is tubular in at least one embodiment.

In some embodiments as shown in FIGS. 3-7, the micropillars arecylinders (FIG. 3), prisms with a rectangular or polygonal base (FIG.4), pyramids (FIG. 5), bumps (FIG. 6), or has a non-traditional shapewith a plurality of bumps and ridges on multiple surfaces that do notdefine a cross-section that is circular, square, polygonal, etc. (FIG.7). Each micropillar can have a circular cross-section (FIG. 8A), squarecross-section (FIG. 8B), rectangular cross-section (FIG. 8C),star-shaped cross-section (FIG. 8D), hexagonal cross-section (FIG. 8E),pentagonal cross-section (FIG. 8F), heptagonal (FIG. 8G), octagonalcross-section (FIG. 8H), nonagonal cross-section (FIG. 8I), decagonalcross-section (FIG. 8J), other polygonal cross-sections, ornon-traditional shaped cross-sections. Each cross-section has a firstdimension h that is the greatest distance between the outer surface ofthe base and the end of the pillar and a second dimension d that is thegreatest distance between two opposite sides (e.g., of the pillar). Forexample, for the circular cross-section the second dimension d is thediameter, for the square d is between two sides, for the rectangle, themajor dimension is between the two shorter sides, for the star, themajor dimension is between two points, for the hexagon the majordimension is between two opposite points. In some embodiments, thesecond dimension d is between midpoints of two opposite sides. In atleast one embodiment, a cross section of the micropillar taken in theradial direction has at least four sides. Embodiments of the presentdisclosure contemplate polygonal cross-sections having all sides ofequal length, combinations of sides of equal length and unequal length,or all sides of unequal length. Embodiments of the present disclosurecontemplate multiple pillars of multiple cross-sectional shapesincluding traditional shapes (e.g. circles, squares, rectangles,hexagons, polygons, etc.) and non-traditional shapes having a perimeterwhere at least a portion of the perimeter is curvilinear. In at leastone embodiment, the micropillars are solid structures, but in otherembodiments they can be hollow structures. In at least one embodiment,each micropillar has a constant cross-section, but in other embodimentsthe micropillars have variable cross-sections. In at least oneembodiment, the plurality of micropillars 54 can be arranged in one ormore particular micropatterns. Although not wishing to be bound bytheory, the micropattern may affect the strength of the frictionalengagement or interlock between the endoprosthesis and the vessel wall.Likewise, the micropattern is dependent upon the desired frictionalengagement or interlock between the micropillars of the endoprosthesisand the tissue. For this reason, in at least one embodiment, aparticular microstructure can be selected that has a micropatterngeometry and dimensions suitable for a particular application (e.g.,implantation site, biological tissue, desired tissue engagementproperties, etc.).

In at least one embodiment, the micropillars in the micropattern allhave the same shape, and in other embodiments, the micropillars vary inshape along the polymeric coating. Thus, in at least one embodiment, themicropattern can include portions where the micropillars have a firstconfiguration and portions where the micropillars have a secondconfiguration. Moreover, embodiments include the polymeric coatinghaving only one micropattern or the polymeric coating having multiplemicropatterns. Thus, the polymeric coating can be tailored to specificstructural characteristics of the body lumen (e.g., a vessel, etc.) anda desired frictional engagement or interlock can be achieved, whileusing a single stent.

In at least one embodiment, the dimension d is between 1 μm and 100 μm.In at least one embodiment, the dimension d is between about 14 μm and18 μm. In at least one embodiment, the dimension d is at least equal tothe dimension h. In at least one embodiment, a ratio of h to d isbetween about 1 and 1.3. In at least one embodiment, two adjacentmicropillars are spaced apart by a distance s (shown in FIG. 3). In atleast one embodiment, the ratio of the spacing s to the dimension d isbetween about 2.1 and 2.4.

In some embodiments, the ends of the protrusions, such as micropillars54, that are furthest away from the outer surface of the base can beshaped to improve tissue attachment. In one or more embodiments, theends can be tapered, pointed, rounded, concave, convex, jagged, orfrayed. The ends of each protrusion (micropillar 54) can include aplurality of pillars on an even smaller scale than micropillars 54.

In at least one embodiment, the protrusions such as micropillars 54 canalso include features such as smooth surfaces, rough surfaces 55 a (FIG.9A), a plurality of bumps 55 b extending outwardly from a surface of themicropillar (FIG. 9B), a plurality of indentations 55 c extendinginwardly from a surface of the micropillar (FIG. 9C), a plurality ofridges 55 d on a surface of the micropillar (FIG. 9D), a tip 55 e at ornear the end of the protrusion that either softer or more rigid than theremainder of the protrusion (FIG. 9E), a frayed tip 55 f (FIG. 9F), andother features that may impart desirable gripping, stiffness, orflexibility characteristics for the endoprosthesis, and any combinationof features thereof. In at least one embodiment, the tip 55 e caninclude a different material than the remainder of the protrusion.

FIG. 3 shows an enlarged view of the polymeric coating 50. In at leastone embodiment, the micropillars are cylinders that each have a diameterd and a height, h measured from an outer surface of the base 56 to a topsurface of the cylinder 58. In at least one embodiment, the diameter dis between 1 μm and 100 μm. In at least one embodiment, the diameter dis between about 14 μm and 18 μm. In at least one embodiment, thediameter d of the micropillar is at least equal to its height h. In atleast one embodiment, a ratio of height h of the micropillar 54 todiameter d of the micropillar is between about 1 and 1.3. In at leastone embodiment, the micropillars each have a lateral surface 59. In atleast one embodiment, two adjacent micropillars are spaced apart. Themicropillars should be spaced apart enough so that the tissue of thebodily vessel can fill the negative space (e.g., void space) between thepillars. If the spacing is too small, the tissue may not be able toactually interlock. In at least one embodiment, the spacing between themicropillars is dependent upon (e.g., may be selected based upon) theparticular type of tissue of the bodily vessel. In at least oneembodiment, the spacing s measured between the centers 57 of onemicropillar and an adjacent micropillar is greater than the diameter dof the one micropillar. In at least one embodiment, the ratio of thespacing s to the diameter d is between about 2.1 and 2.4.

In at least one embodiment, the micropillars are spaced apartequidistantly in the micropattern. In at least one embodiment, themicropattern of micropillars is a rectangular array. In at least oneembodiment, the micropattern is a grid pattern. In other words, in themicropattern, the micropillars are arranged in rows and columns in themicropattern, wherein the rows and columns may or may not beperpendicular. In one or more embodiments, each micropillar has alongitudinal axis and the micropillars are axially aligned in at leastone of the axial direction (e.g., arranged in a row parallel to alongitudinal axis of a stent) and the circumferential direction of theendoprosthesis (e.g., arranged in a row extending circumferentiallyaround a longitudinal axis of a stent). In at least one embodiment, themicropattern of micropillars includes any or all of the featuresdescribed in this paragraph. In some embodiments, like the embodimentsshown in 10A and 10B, the micropattern may cover only a portion of thebase 52 rather than the entire base 52. The micropattern of micropillarsmay be helically disposed on the base 52, as shown in FIG. 10A. In oneor more embodiments, as shown in FIG. 10B, a first micropattern may bedisposed longitudinally along the base 52 and a second micropattern isdisposed circumferentially about the base so that the micropattern formsa “window pane”-like configuration.

Regarding the material used for the polymeric coating 50, it isimportant that the material be flexible enough to create an effectiveinterlock with the tissue and be able to withstand the processing forcreating the polymer coating 50. Examples of acceptable materialsinclude, but are not limited to, flexible silicones, hydrogels, andother suitable elastomers, such as synthetic rubbers. Other acceptablematerials include any flexible, biocompatible, and non-biodegradablepolymer. In at least one embodiment, the polymeric coating 50 mayinclude proteins capable of engaging the tissue wall in a biochemicalmanner. In at least one embodiment, the polymeric coating 50 may includeat least one therapeutic agent. In other embodiments, an additionalcoating may be applied to the polymeric coating 50 that includes atherapeutic agent. A therapeutic agent may be a drug or otherpharmaceutical product such as non-genetic agents, genetic agents,cellular material, etc. Some examples of suitable non-genetictherapeutic agents include but are not limited to: anti-thrombogenicagents such as heparin, heparin derivatives, vascular cell growthpromoters, growth factor inhibitors, paclitaxel, etc. Where an agentincludes a genetic therapeutic agent, such a genetic agent may includebut is not limited to: DNA, RNA and their respective derivatives and/orcomponents; hedgehog proteins, etc. Where a therapeutic agent includescellular material, the cellular material may include but is not limitedto: cells of human origin and/or non-human origin as well as theirrespective components and/or derivatives thereof.

In a preferred embodiment, the micropillars 54 and the base 56 areformed from the same material. In one or more embodiments, themicropillars 54 are formed from one material and the base 56 is formedfrom a different material. In one or more embodiments, the micropillars54 are formed with layers of material, and these layers can be the samematerial or can be different materials depending on the characteristicsrequired for the desired frictional engagement of the endoprosthesiswith the vessel wall. In at least one embodiment, two micropillars 54 ofa polymer coating 50 may be formed from the same or different materials.

Because the endoprosthesis 20 has improved frictional engagement withthe tissue wall when inserted into a lumen of the patient, removal ofthe stent may be more difficult with some traditional removaltechniques. In at least one embodiment, shown in FIG. 1, theendoprosthesis 20 is provided with a suture or removal loop 55 on oneend of the stent. In at least one embodiment, the removal loop 55 isprovided on a distal end of the stent. It should be noted thatreferences herein to the term “distal” are to a direction away from anoperator of the devices of the present disclosure, while references tothe term “proximal” are to a direction toward the operator of thedevices of the present disclosure. While sutures or removal loops arewell known in the art for removing endoprosthesis, typically sutures orremoval loops are provided on the proximal end of the stent, in otherwords the closest end to the practitioner. Here, the suture or removalloop is applied to the opposite end of the endoprosthesis. In at leastone embodiment, the practitioner grabs the loop from inside theendoprosthesis, and by applying an axial force to the loop, the distalend of the endoprosthesis is pulled through the lumen of theendoprosthesis itself. Thus, the micropillars are peeled away from thevessel wall while the stent is flipped inside out to remove theendoprosthesis. In other embodiments, the practitioner may grab the loopfrom outside the endoprosthesis or at an end of the endoprosthesis.

To manufacture the endoprosthesis 20, several methods can be employed.The polymeric coating 50 can be molded separately from the stent andthen adhered to the stent with an adhesive layer 60 between the outersurface of the endoprosthesis and the base of the polymeric coating.Polymeric material can be injected into a mold with the inverse of themicropattern to create the polymeric coating. Also, the polymericmaterial can be pulled through a mold using a vacuum pump system. In atleast one embodiment, the polymeric coating can be created using softlithography techniques. In one or more embodiments, etching techniquescan be used to create the coating, wherein material is taken away from alayer of the coating material to create the micropattern of thepolymeric coating 50. In yet another embodiment, a technique called hotembossing can be used, which involves stamping partially cured polymerinto the desired shape of the polymeric coating and then curing itbefore it is applied to the stent. Stamping may or may not include theuse of a solvent.

In at least one embodiment, as shown in FIG. 11, the coating 50 can bemolded as a substantially tubular structure with a lumen defined by thebase of the coating. An adhesive layer 60 can be applied to either thestent or to at least a portion of the inner surface of the base of thecoating. In at least one embodiment, the adhesive layer 60 maysubstantially cover the entire inner surface of the base of the coating.The stent 40 can be inserted into the lumen of the coating 50. In atleast one embodiment, heat and/or pressure may be applied to ensureproper adhesion of the coating 50 to the stent 40 via the adhesive layer60. The adhesive layer may include silicone coatings, other suitableadhesives, or priming solutions that enable the coating to adhere to themetal stent (or stent coating thereon). In one or more embodiments, asshown in FIG. 12, rather than being molded as a tubular structure, thecoating 50 can be molded as a strip attached to the outer surface 44 ofthe stent 40. In some embodiments, the strip can be applied as perimeterstrips attached circumferentially about at least a portion of thecircumferential perimeter of the stent. In some embodiments, the stripcan be a longitudinal strip attached to the stent in a longitudinaldirection. In some embodiments, the stent can be helically wrapped aboutthe stent, as shown in FIG. 12. In some embodiments the coating may beapplied as a single strip or as multiple strips. Where the coating isapplied as multiple strips, directly adjacent strips may abut oneanother or may be spaced apart from one another. In at least oneembodiment, the strips may be partial tubular structures that extendalong the length of the stent but only cover a portion of thecircumference of the stent. In some embodiments, a portion of stent 40may be exposed. An adhesive layer 60 can be applied to either the stentor to at least a portion of the base of the coating. In at least oneembodiment, heat and/or pressure may be applied to ensure properadhesion of the coating 50 to the stent 40 via the adhesive layer 60. Inat least one embodiment, discrete micropatterns of micropillars can beformed on and/or attached directly to either the stent 40 or thepolymeric coating 50.

In one or more embodiments, the polymeric coating 50 can be formed bydip-coating the stent 40 in the coating material without needing anadditional adhesive layer to connect the coating 50 to the stent 40. Forinstance, the stent 40 can be inserted into a mold, which includes acavity and a tubular member. The cavity is defined by an inner wall ofmold, which is an inverse of the desired micropattern. The stent 40rests on the tubular member such that the inner surface of the stent isdisposed about the tubular member. The mold with the stent 40 can bedipped into the coating material so that the coating material fills themold and attaches to the stent 40. In some embodiments, temperaturechanges and/or pressure changes may be applied to the mold to cure thecoating material. Once the coating material cures to form the polymercoating 50, the endoprosthesis 20 can be removed from the mold.Alternatively, the polymer coating 50 can be injection molded onto thestent using a similar mold. The coating material is injected into themold rather than the mold being dipped into the coating material.

Micropatterns of the types described herein may aid in reducing thebuildup of granulation tissue at, for example, stent ends. For example,micropatterned polymer coatings (e.g., pads, stent end coverings etc.)may be applied to stents or other devices to reduce or eliminate growthof undesirable granulation tissue. In one or more embodiments,micropatterned polymer coatings may be, for example, specificallydesigned to cushion the covered portion of the device and promote wouldhealing through administration of appropriate growth factors and/orfacilitation of cell migration across a recurring wounded area. Althoughnot wishing to be bound by theory, it is believed that cells such asfibroblasts, endothelial cells, and muscle cells actively sense both theexternal loading applied to them (outside-in signaling) and thestiffness of their surroundings (inside-out signaling) and respond tothese stimuli with changes in adhesion, proliferation, locomotion,morphology, and synthetic profile. More details regarding this areprovided by Throm Quinlan et al., “Combining dynamic stretch and tunablestiffness to probe cell mechanobiology in vitro,” PLoS One, 2011;6(8):e23272, which is incorporated herein by reference in its entirety.Also incorporated by reference in its entirety is Yoon et al., “Passivecontrol of cell locomotion using micropatterns: the effect ofmicropattern geometry on the migratory behavior of adherent cells,” LabChip, 2012 Jul. 7; 12(13):2391-2402, which indicates that the amount andgradient of physical spatial cues imposed by changing the width anddivergence angle of micropatterns make it possible to control the rateand direction of cell migration in a passive way, the result of whichoffer a potential for reducing the healing time of open wounds.

In one or more embodiments, a micropatterned structure (e.g., amicropatterned polymer coating 50, a micropatterned stent end covering50A, 50B, etc.) may be expected to reduce the formation of granulationtissue at or near the stent ends by (1) mechanically stimulating cellmigration (due to, for example, micropattern topography) around a woundsite; (2) adding a protecting polymer barrier between the stent ends(e.g., stent ends that include wire, etc.) and luminal tissue; and/or(3) potentially administering growth factors and/or proteins to theirritated area in order to promote wound healing. For example, factorscould be administered that enhance one or more aspects of wound healingto improve the likelihood of complete healing. In one or moreembodiments, factors could be administered that specifically move alongthe phases of wound healing such that granulation tissue building wouldbe reduced or eliminated (e.g., relative to a similar embodiment withoutuse of the factor, relative to a similar embodiment without the use of amicropatterned stent end covering).

For example, a graphical representation of the cellular characteristicsof the wound healing process is presented by de la Torre et al. (de laTorre et al., “Chronic Wounds,” MedScape Reference—Drugs, Diseases andProcedures, available athttp://emedicine.medscape.com/article/1298452-overview#showall) (lastaccessed Mar. 7, 2013)), incorporated by reference in its entirety,including different types of cell involvement over the course of woundhealing. The progression of specific cell, matrix, or processes eachmaximize in the following order according to de la Torre et al.:platelets, neutrophilia, macrophagen, lymphocytes, capillaries andepithelium, fibroblasts, and collagen. De la Torre indicates that in thesecond stage of the inflammatory phase, leukocytes supplant platelets asthe dominant cell type, attracted by chemotaxis (chemical signalingthrough growth factor/protein concentrations). White blood cells are thepredominant cells for the first 3 days after wounding and after 24-36hours, circulating monocytes enter the wound and mature into tissuemacrophages. These cells debride the wound on the microscopic level andproduce a wide variety of important substances, such as IL-1 and basicfibroblast growth factor (bFGF). IL-1 stimulates the proliferation ofinflammatory cells and promotes angiogenesis through endothelial cellreplications. bFGF is a chemotactic and mitogenic factor for fibroblastsand endothelial cells. Two to three days after healing, fibroblastsmigrate inward from wound margins over the fibrinous matrix establishedduring the inflammatory phase. During the first week, fibroblasts beginproducing glycosaminoglycans and proteoglycans, the ground substance forgranulation tissue, as well as collagen, in response tomacrophage-synthesized bFGF and TGF-β, as well as PDGF (growth factorsthat influence cell behavior).

In at least one embodiment, a micropatterned structure (e.g., a polymercoating 50, a stent end covering 50A, 50B, etc.), as described herein,may assist with the proliferation and remodeling stages of woundhealing, but could also be used to deliver or promote growth factorsduring the initial inflammatory stage (e.g., if applied early enough anddesigned to do so).

In at least one embodiment, an endoprosthesis 20 may include a stenthaving one or more stent ends 46, 48 having a covering 50A (e.g., astent end covering) attached thereto having a micropatterned surfacethat may extend circumferentially around at least a portion of a stentend 46 and may optionally extend longitudinally beyond (e.g.,cantilever) a stent end 46.

For example, FIGS. 13A-13D depict schematics of a portion of anendoprosthesis 20 having a stent 40 that has a stent end 46 having acovering 50A attached thereto. Covering 50A extends circumferentiallyaround stent end 46 (e.g., FIG. 13C). In one or more embodiments,covering 50A extends circumferentially only partially around stent end46. As shown, covering 50A may cover the entire area (e.g., the entirecircumference of the stent end) around the stent end 46 where, forexample, granulation tissue buildup would otherwise be expected.

In some embodiments, the micropatterned covering 50A may extend beyondthe end of the endoprosthesis (e.g., extending in the manner of acantilever). In some embodiments, the micropatterned covering 50A mayhave a varying radial thickness, which may allow for the covering todouble back into the end of the stent, thereby forming a thicker cushionnear and around the stent end 46 (e.g., FIG. 13D).

In one or more embodiments, the micropatterned covering may be used at aplurality of stent ends 46, 48 (e.g., both ends of a tubular stent, twoor more ends of a bifurcated stent, etc.).

The use of a micropatterned stent end covering 50A as described hereinmay better protect the ends of the stent (and better protect the luminaltissue near the stent ends) and may promote wound healing. Thus, damagedluminal tissue (e.g., gastrointestinal tissue, tracheal tissue, etc.)may heal property in a more timely manner, which may reduce excessivegrowth of delicate granulation tissue.

In one or more embodiments, covering 50A may be applied to any of a widevariety of materials of endoprosthesis construction (e.g., metal,polymer, etc.). In one or more embodiments, a micropatterned coveringfor use in reduction of granulation tissue growth may be utilized on anyof a wide variety of long-term implant devices that may generategranulation tissue by repeated trauma. In one or more embodiments, anendoprosthesis having a micropatterned stent end covering 50A may beplaced in, for example, a gastrointestinal tract and its branches (e.g.,esophageal, duodenal, biliary, colonic, etc.) or an airway.

FIGS. 13A-13D depict basic schematics of where the micropatterned stentend coverings 50A may be disposed in relation to an endoprosthesis.Covering 50A may include any of the one or more micropatterns describedherein and the micropillars of the covering's micropattern may includeany of the one or more micropillar structures and dimensions describedherein. For example, covering 50A may include one micropattern or aplurality of micropatterns (e.g., having the same or different geometricarrangements, having the same or different density of micropillars perarea of base, etc.). Covering 50A may include uniformly shaped and sizedmicropillars or may include micropillars having two or more shapesand/or two or more dimensions. The microscale features (e.g.,micropillars) may take any of a wide variety of forms (e.g., shapes,dimensions) in order to effectively stimulate cells to migrate (or topromote other biological responses (e.g., tasks) that aid in woundhealing.

Although ingrowth and granulation tissue buildup is commonly observednear stent ends, the micropatterned coverings 50A of the presentdisclosure may be disposed in a wide variety of locations along anendoprosthesis. In one or more embodiments, a micropattern used incovering 50A may be applied to other portions of an endoprosthesis(e.g., a medial portion disposed between the stent ends, the perimeterof a radial-facing opening, etc.), if desired.

In at least one embodiment, a stent end covering 50A having amicropatterned surface may be deployed in a body lumen separately froman endoprosthesis, wherein the stent end covering may be deployed in abody lumen followed by deployment of an endoprosthesis wherein a stentend is disposed within at least a portion of the stent end covering(e.g., the stent end covering may be biased between the stent end andthe wall of the body lumen).

For example, in FIGS. 14A-14B, micropatterned stent end coverings 50Bmay take the form of bands (e.g., circular bands, ring-shaped bands,bands having one or more radial thicknesses, etc.) that may be placedwith a body lumen before stent deployment (e.g., FIG. 14A), such thatthe stent ends may be deployed onto the bands (e.g., with the each banddisposed between a stent end and the luminal wall). In at least oneembodiment, each of two micropatterned stent end coverings 50B may bedisposed within a body lumen such that a portion of the body lumen to bestented is located between the micropatterned stent end coverings 50B. Astent may then be disposed within the body lumen such that therespective ends of the stent are deployed onto the micropatterned stentend coverings (e.g., micropatterned pads) as shown in FIG. 14B.

In the one or more embodiments of FIGS. 14A-14B, because the bands aredeployed separate from the endoprosthesis, the constraints on design ofthe band are fewer. That is, the dimensions and/or material propertiesof each band may be such that delivery while attached to anendoprosthesis is impossible or impractical. For example, the bandsdepicted in FIGS. 14A-14B may be allowed to be thicker and moreeffective as protective pads (e.g., relative to the coverings 50A ofFIG. 13A, etc.) and need not be deployed with the endoprosthesisthrough, for example, a sheath delivery system. This embodiment maylimit use, however, depending on the anatomy in which the endoprosthesisis deployed (e.g., the anatomy being stented).

Herein, all of the features, qualities, characteristics, functions, anddescriptions of polymer coating 50 apply to stent end coverings 50A,50B, unless the context indicates otherwise.

Stent end coverings 50A, 50B may be manufactured in any of a widevariety of methods including, but not limited to, lithography, etching,and particle deposition.

In one or more embodiments, the stent end covering 50A, 50B may bemanufactured separately prior to application (e.g., adherence,attachment, etc.) to a medical device (e.g., stent, etc.). In one ormore embodiments, a medical device (e.g., a stent, etc.) may incorporatea micropattern near the ends of the device (e.g., stent ends). Forexample, in one or more embodiments in which a portion (e.g., an endportion) of a medical device is made of an appropriate material (e.g.,silicone, silicone coating, biocompatible polymer or metal, etc.) formicropatterning for reduction of granulation tissue buildup, then themicropattern may be directly incorporated into the structure of themedical device (e.g., stent, etc.).

In one or more embodiments, stent end coverings 50A, 50B may include anyof a wide variety of materials of construction including, but notlimited to, the materials described herein for bases and/ormicropillars, flexible polymers, rigid polymers, biocompatible polymers,metals, and any other suitable material known to one of skill in theart. In some embodiments, a stent end covering may include a material ofconstruction useful for, for example, cell migration and growth factordelivery.

As mentioned herein with regard to FIGS. 9E and 9F, a micropillar 54 mayinclude a tip 55 e at or near the end of the protrusion that eithersofter or more rigid than the remainder of the protrusion (FIG. 9E), afrayed tip 55 f (FIG. 9F), and other features that may impart desirablegripping, stiffness, or flexibility characteristics for theendoprosthesis, and any combination of features thereof. The tip 55 emay include a different material than the remainder of the protrusion.

In one or more embodiments of the present disclosure, a micropillar 54may include a tip that includes a hygroscopic material (e.g., ahygroscopic polymer such as nylon, acrylonitrile butadiene styrene(ABS), polycarbonate, cellulose, and poly(methyl methacrylate), etc.)and includes a geometry and/or a material composition that mayfacilitate anchoring the micropillar in tissue. Anchoring a micropillarin tissue may be useful for reducing or eliminating migration of themicropatterned item.

As shown in FIGS. 15, 16, and 17, micropillar 54 may include a tip suchas an anchor 80 that has a maximum diameter that is larger than thediameter of the micropillar where the micropillar meets the anchor.Anchor 80 may take any of a wide variety of geometries. In one or moreembodiments, anchor 80 takes a teardrop shape (e.g., FIG. 15) or a coneshape (e.g., FIGS. 16, 17) having an apex 82 that has a diameter smallerthan the diameter of the micropillar where the micropillar meets theanchor.

In one or more embodiments, anchor 80 may be constructed and arranged topenetrate a mucosal membrane with minimal irritation, given the size andaspect ratio of the anchor and micropillar. Once inside the mucosalmembrane, the hygroscopic polymer of anchor 80 may absorb surroundingmoisture and swell. In at least one embodiment, this increase indiameter will allow micropillars to anchor in the mucosal membrane,which may increase traction and resist migration of the micropatternedpolymer coating. For example, in FIGS. 16 and 17, a hygroscopic polymeranchor 80 may have a relatively narrow profile in FIG. 16 which mayallow penetration in a mucosal membrane and anchor 80 may have arelatively wide profile in FIG. 17 after the hygroscopic polymer swells.Swelled anchor 80 may then act as a fixation mechanism, such as a barb,to secure the micropillar to the mucosal membrane.

Manufacturing of micropillars 54 having anchors 80 may be accomplishedin a wide variety of manners. For example, the micropillars may be castor molded out of a firm polymer resin to maintain columnar strength,followed by dip coating the micropillars in a hygroscopic polymer toallow a tip (e.g., a fine point tip) to be formed. Other methods offorming a micropillar with an anchor are contemplated.

In one or more embodiments of the present disclosure, a micropatternedpolymer coating 50 may be used to provide an adhesive quality to medicaldevices (e.g., medical devices to treat obesity). A jejunal liner, whichmay be used to treat obesity, may include a sleeve having an anchorportion (e.g., a flared end, a portion with barbs, etc.) that isanchored in a pylorus and prevents food absorption in the duodenum andpart of the jejunum. Jejunal liners may be commercially available fromGI Dynamics (Lexington, Mass.). Barbs have been used to anchor a jejunalliner in place. In one or more embodiments, an adhesive micropatternedpolymer coating 50 may be used to anchor a sleeve at or near a patient'spylorus and may be used in conjunction with or as an alternative tobarbs. At least a portion of an outer surface of a jejunal liner sleevemay be covered with an adhesive micropatterned polymer coating 50.

Various portions of a jejunal liner may include an adhesivemicropatterned polymer coating 50. For example, an adhesivemicropatterned polymer coating 50 may cover an entire outside surface ofthe sleeve (e.g., wherein the liner lacks an anchor portion and thesleeve is to be adhered to the duodenum and jejunum, etc.), may cover anentire outside surface of an anchor portion (e.g., a flared portion ofthe sleeve), may cover all or a portion of a sleeve anchored in theesophagus, may cover a sleeve having a stent thereon, may cover aportion of the outside surface of the sleeve (e.g., wherein the sleeveis otherwise adhered to the small intestine with a balloon, etc.). Inone or more embodiments, a sleeve having a micropatterned polymercoating 50 thereon (e.g., for anchoring) may be implanted distal of thepapilla of Vaters.

The micropatterned polymer coatings 50 of the present disclosure may beutilized on any of a wide variety of medical devices (e.g., for treatingobesity, etc.). For example, stents have been used for treating leaksafter bariatric surgery. In one or more embodiments, a stent (or aportion thereof) may have an adhesive micropatterned polymer coating 50thereon, which may reduce or prevent migration (e.g., of the stent). Inone or more embodiments, gastric banding may include an adhesivemicropatterned polymer coating 50 thereon to reduce or preventmigration.

Another aspect of the present disclosure relates to a patch, e.g., forthe treatment of a wound. In one or more embodiments, a wound patch mayinclude one or more polymer coatings (e.g., micropatterned polymercoatings) that may facilitate wound healing. In at least one embodiment,wound patches may be utilized in a body lumen (e.g., gastrointestinaltissue).

With reference to FIG. 18, a micropatterned wound patch 70 may beadhered to tissue 72 (e.g., a gastrointestinal wall, etc.) near toand/or circumscribing a wound site 74. Wound patches of the presentdisclosure may be useful for wound sites in any portion of a body (e.g.,body lumen, skin, body cavity, etc.).

In one or more embodiments, a wound patch 70 may include one or moreadhesive micropatterned polymer coatings 76 on the edges of the woundpatch 70, wherein the micropatterned polymer coatings 76 are configuredand arranged to adhere to gastrointestinal (GI) tissue 72. In one ormore embodiments, a wound patch 70 can take any of a wide variety ofshapes and can be structured such that the micropatterned polymercoatings 76 for adhering to tissue 72 are arranged on, for example, atleast two sides of a wound site 74. That is, the adhesive micropatternedpolymer coating 76 may form a type of perimeter, or portion thereof,that extends entirely or partially around a wound site 74. In at leastone embodiment, the adhesive micropatterned polymer coating 76 holds thewound patch 70 in place over the wound (e.g., the wound patch extendsover the wound site 74) during the healing process, thereby preventingthe wound patch 70 from being dislodged within the GI tract as well asprotecting the wound 74 from any detrimental effects present in the GIenvironment. In at least one embodiment, a wound patch 70 can hold thetissue of a wound 74 closer together (e.g., help close the wound) duringhealing, which may reduce the time required for healing.

Many configurations of one or more micropatterned polymer coatings on awound patch are envisioned in the present disclosure. For example, inFIGS. 19A-19C, three examples of micropattern arrangements are provided.For each wound patch 70 depicted, one or more adhesive micropatternedpolymer coatings 76 are arranged on or near one or more edges of thewound patch 70. A plurality of adhesive micropatterned polymer coatings76 may be arranged along a perimeter of a wound patch 70, a continuousadhesive micropatterned polymer coating 76 may extend around the entireperimeter of a wound patch 70, or two adhesive micropatterned polymercoatings 76 may be disposed on at least two ends/edges of a wound patch70. Many other arrangements are possible and may be envisioned by one ofskill in the art.

In one or more embodiments, a region of a wound patch 70 to be locateddirectly over a wound 74 may also include a wound-coveringmicropatterned polymer coating 78, in at least one embodiment. Forexample, a micropatterned polymer coating may include a micropatternthat can promote cell migration. Stimulation of tissue of the wound site74 by the micropattern may result in a higher cell count at the woundsite 74, which can expedite healing in at least one embodiment. In oneor more embodiments, the wound-covering micropatterned polymer coating78 over the wound site 74 may be structured and arranged to controlother aspects of cell behavior by, for example, releasing growthfactors, releasing therapeutic agents, releasing proteins, etc. In someembodiments, the micropatterned polymer coating 78 disposed over a woundsite 74 may include the same micropattern (e.g., the same micropillararea density, micropillar geometric arrangement/pattern, micropillardimensions, micropillar shape, micropillar composition, etc.) as theadhesive micropatterned polymer coating 76 used for adhesion to tissue.In one or more embodiments, these micropatterns 76, 78 may differ in oneor more ways (e.g., area density, pattern, dimensions, shape,composition, etc.), without limitation.

Also depicted in the examples of micropattern arrangements in FIGS.19A-19C are wound-covering micropatterned polymer coatings 78, which cantake any shape (e.g., geometric, non-geometric, etc.) in at least oneembodiment. Each of the wound patches 70 of FIGS. 19A-19C includes onewound-covering micropatterned polymer coating 78, but a plurality ofwound-covering micropattern polymer coatings 78 can be used in one ormore embodiments. Many other arrangements of wound-coveringmicropatterned polymer coatings may be envisioned by one of skill in theart.

In one or more embodiments, a wound patch 70 can include one or moreradiopaque portions (e.g., markers) for improved visualization (e.g.,via fluoroscopy, etc.), improved positioning accuracy during delivery,and/or improved monitoring after delivery. Each radiopaque marker can bedisposed at a strategic location on a wound patch 70 depending on thewound patch geometry and target wound site anatomy and would be viewablebefore, during, and after the wound patch deployment procedure.

In one or more embodiments, a plurality of wound patches 70 can be usedto achieve increased tissue adhesion and/or increased cell stimulation.

A wound patch 70 that includes one or more micropatterned polymercoatings 76, 78 may be useful in a wide variety of applicationsincluding treatment of post-biopsy bleeding, ulcers, variceal bleeding,fistula, etc.

Deployment of a wound patch 70 of the present disclosure may beaccomplished in any of a wide variety of ways. As depicted in FIGS.20A-20C, in one or more embodiments, a wound patch 70 (e.g., FIG. 20A)can be rolled (e.g., FIG. 20B) and placed within a delivery system(e.g., an endoscopic delivery system, a TTS delivery system, etc.), anddeployed through an endoscope 80 for use in a body lumen (e.g., GItract). A rolled wound patch 70 may be advanced through an endoscope 80using, e.g., a pusher or plunger. When the wound patch 70 is in place(confirmed by, for example, fluoroscopy), the rolled wound patch 70 maybe pushed forward (distally) or the endoscope may be pulled backward(proximally) to deploy the wound patch 70 (e.g., FIG. 20C).

In one or more embodiments, a wound patch 70 may be rolled around anexpansive or inflatable mandrel or balloon within a delivery system,wherein the mandrel or balloon would press the wound patch 70 againstthe tissue 72 (e.g., GI wall) upon or after deployment to initiateadhesion of the adhesive micropatterned polymer coating 76 to the tissue72 (e.g., GI wall).

In one or more embodiments, the wound patch 70 can include a widevariety of materials of construction, including flexible polymers, wovenmesh, etc. The micropatterned polymer coatings 76, 78 on wound patches70 may be made from any of a wide variety of materials in order toprovide an effective structure for tissue adhesion and cell migrationincluding, but not limited to, those materials identified herein withregard to polymer coating 50. The micropatterned polymer coatings may bemanufactured in any of the ways described herein with regard to othermicropatterned polymer coatings. In one or more embodiments, a woundpatch 70 can include a separate backing with micropatterned polymercoatings 76, 78 attached thereto. In one or more embodiments, the woundpatch 70 can be an integral piece of material having micropatternsformed thereon or incorporated therein.

The above disclosure is intended to be illustrative and not exhaustive.This description will suggest many variations and alternatives to one ofordinary skill in this art. All these alternatives and variations areintended to be included within the scope of the claims where the term“comprising” means “including, but not limited to.” Those familiar withthe art may recognize other equivalents to the specific embodimentsdescribed herein which equivalents are also intended to be encompassedby the claims.

Further, the particular features presented in the dependent claims canbe combined with each other in other manners within the scope of thepresent disclosure such that the present disclosure should be recognizedas also specifically directed to other embodiments having any otherpossible combination of the features of the dependent claims.

A description of some exemplary embodiments of the invention iscontained in one or more of the following numbered statements:

Statement 1. An endoprosthesis having an expanded state and anunexpanded state, the endoprosthesis comprising:

-   -   a stent, wherein the stent has a first end, a second end, an        inner surface extending from the first end to the second end and        defining a lumen, an outer surface extending from the first end        to the second end, and a thickness defined between the inner        surface and the outer surface; and    -   a stent end covering disposed at one of the first and second        ends, the stent end covering comprising:        -   a polymeric coating comprising a base and a plurality of            protrusions, the base comprising a first major surface            facing the outer surface of the stent, the base further            comprising a second major surface from which each of the            plurality of protrusions extends outwardly, the first major            surface opposing the second major surface, wherein the            protrusions are arranged in a micropattern.

Statement 2. The endoprosthesis of statement 1, wherein the stent endcovering is adhered to the outer surface of the stent.

Statement 3. The endoprosthesis of statement 1 or statement 2, whereinthe stent end covering is adhered to the inner surface of the stent.

Statement 4. The endoprosthesis of any one of statements 1-3, whereinthe stent end covering extends circumferentially and entirely around oneof the first and second ends.

Statement 5. The endoprosthesis of any one of statements 1-4, whereinthe stent end covering extends circumferentially and partially aroundone of the first and second ends.

Statement 6. The endoprosthesis of any one of statements 1-5, whereinthe stent end covering extends longitudinally from a location betweenthe first and second ends to a location that is not between the firstand second ends.

Statement 7. The endoprosthesis of any one of statements 1-6, wherein atleast a first portion of the stent end covering has a radial thicknessgreater than the thickness of the stent at the stent end that is nearestto the stent end covering.

Statement 8. The endoprosthesis of statement 7, wherein at least asecond portion of the stent end covering has a radial thickness lessthan the radial thickness of the first portion of the stent endcovering.

Statement 9. The endoprosthesis of any one of statements 1-8, whereinthe stent end covering comprises:

-   -   a first stent end covering and a second stent end covering,        wherein one of the first and second stent end coverings is        disposed at the first end and one of the first and second stent        end coverings is disposed at the second end.

Statement 10. A method of manufacturing an endoprosthesis comprising:

-   -   forming a stent end covering comprising a polymeric coating,        wherein the polymeric coating comprises a base and a plurality        of protrusions, the base comprising a first major surface facing        the outer surface of the stent, the base further comprising a        second major surface from which each of the plurality of        protrusions extends outwardly, the first major surface opposing        the second major surface, wherein the protrusions are arranged        in a micropattern;    -   providing a stent having a first end, a second end, an inner        surface extending from the first end to the second end and        defining a lumen, an outer surface extending from the first end        to the second end, and a thickness defined between the inner        surface and the outer surface; and    -   contacting the stent end covering with one of the first and        second ends of the stent.

Statement 11. The method of statement 10, wherein the contacting furthercomprises contacting the stent end covering with the outer surface ofthe stent.

Statement 12. The method of statement 10 or statement 11, wherein thecontacting further comprises contacting the stent end covering with theinner surface of the stent.

Statement 13. The method of any one of statements 10-12, wherein thecontacting comprises disposing the stent end covering circumferentiallyand entirely around one of the first and second ends.

Statement 14. The method of any one of statements 10-13, wherein thecontacting comprises disposing the stent end covering wherein the stentend covering extends longitudinally from a location between the firstand second ends to a location that is not between the first and secondends.

Statement 15. The method of any one of statements 10-14, wherein themethod further comprises:

-   -   disposing the stent end covering within a body lumen, wherein        disposing the stent end covering within the body lumen occurs        before contacting the stent end covering with one of the first        and second ends of the stent.

Statement 16. The method of any one of statements 10-15, wherein thecontacting comprises deploying the stent within the body lumen, whereinthe stent end covering is disposed between a lumen wall of the bodylumen and one of the first and second ends of the deployed stent.

Statement 17. The method of any one of statements 10-16, wherein formingthe stent end covering comprising the polymeric coating comprises usinga mold having an inverse of the micropattern and injecting a polymericmaterial into the mold.

Statement 18. The method of any one of statements 10-17, wherein thecontacting comprises applying an adhesive to at least one of a surfaceof the base and the outer surface of the stent.

Statement 19. A method of using an endoprosthesis comprising:

-   -   providing a stent end covering comprising a polymeric coating,        wherein the polymeric coating comprises a base and a plurality        of protrusions, the base comprising a first major surface facing        the outer surface of the stent, the base further comprising a        second major surface from which each of the plurality of        protrusions extends outwardly, the first major surface opposing        the second major surface, wherein the protrusions are arranged        in a micropattern;    -   providing a stent having a first end, a second end, an inner        surface extending from the first end to the second end and        defining a lumen, an outer surface extending from the first end        to the second end, and a thickness defined between the inner        surface and the outer surface; and    -   disposing the stent end covering within a lumen; and    -   after disposing the stent end covering within a lumen,        contacting the stent end covering with one of the first and        second ends of the stent.

Statement 20. The method of statement 19, wherein the contactingcomprises deploying a stent within the lumen.

This completes the description of the preferred and alternateembodiments of the present disclosure. Those skilled in the art mayrecognize other equivalents to the specific embodiment described hereinwhich equivalents are intended to be encompassed by the claims attachedhereto.

The invention claimed is:
 1. An endoprosthesis having an expanded state and an unexpanded state, the endoprosthesis comprising: a stent having an inner surface and an outer surface; and a stent covering disposed on at least a portion of the outer surface of the stent, the stent covering including a polymeric coating having a base and a plurality of protrusions extending outwardly from the base, wherein the protrusions include a firm polymer resin columnar portion and a hygroscopic polymer coating, wherein the protrusions are arranged in a micropattern, wherein the protrusions are configured to expand from a first profile to a second profile.
 2. The endoprosthesis of claim 1, wherein a diameter of each of the protrusions in the second profile is larger than a diameter of the protrusions in the first profile.
 3. The endoprosthesis of claim 1, wherein the protrusions are configured to move from the first profile to the second profile when the protrusions are placed in a moist environment.
 4. The endoprosthesis of claim 1, wherein the columnar portions of the protrusions extend from the base and a tip portion is disposed on each columnar portion, wherein a diameter of the tip portion is greater than a diameter of the columnar portion in the second profile.
 5. The endoprosthesis of claim 4, wherein the tip portions are cone shaped.
 6. The endoprosthesis of claim 1, wherein the stent covering extends over an entirety of the outer surface of the stent.
 7. The endoprosthesis of claim 1, wherein the stent extends along a longitudinal axis from a first end to a second end, the stent having a middle portion between the first and second ends, wherein the stent covering extends over one or both of the first and second ends, but not the middle portion.
 8. The endoprosthesis of claim 7, wherein the stent covering extends longitudinally beyond the first or second ends of the stent.
 9. The endoprosthesis of claim 8, wherein the stent covering doubles back into a lumen of the stent.
 10. The endoprosthesis of claim 1, wherein the stent covering is adhered to the outer surface of the stent.
 11. An endoprosthesis having an expanded state and an unexpanded state, the endoprosthesis comprising: a tubular stent, wherein the stent has an inner surface, an outer surface, a first end, a second end, and a thickness defined between the inner surface and the outer surface, wherein the stent has a plurality of openings extending through the thickness; and a polymeric coating adhered to the outer surface of the stent, the polymeric coating comprising a base and a plurality of protrusions extending outwardly from the base, each protrusion having a columnar portion extending from the base and a distal tip portion disposed on the columnar portion, wherein the columnar portion is made of a first material and the distal tip portion is made of a second material different from the first material, wherein the protrusions are arranged in a micropattern, wherein the base covers the openings of the stent; wherein the distal tip portions of the protrusions are configured to expand from a first profile to a second profile.
 12. The endoprosthesis of claim 11, wherein a diameter of the distal tip portion of each of the protrusions in the second profile is larger than a diameter of the protrusions in the first profile.
 13. The endoprosthesis of claim 11, wherein the protrusions are configured to move from the first profile to the second profile when the protrusions are placed in a moist environment.
 14. The endoprosthesis of claim 11, wherein the protrusions include a hygroscopic polymer.
 15. The endoprosthesis of claim 14, wherein the columnar portions of the protrusions include a firm polymer resin and the distal tip portions include a hygroscopic polymer coating.
 16. An endoprosthesis having an expanded state and an unexpanded state, the endoprosthesis comprising: a tubular stent having an inner surface and an outer surface; and a stent covering disposed on at least a portion of the outer surface of the stent, the stent covering including a polymeric coating having a base and a plurality of protrusions extending outwardly from the base, wherein the protrusions include a firm polymer resin columnar portion and a hygroscopic polymer coating, wherein the protrusions are arranged in a micropattern. 